The most serious clinical consequences of cancer are due to the metastatic property of the malignant cell. Control of metastases, therefore, remains the most important, and admittedly, still the most difficult goal of cancer therapy. Recently, the therapeutic potential of liposomes containing cytotoxic drugs or biological effector molecules has been explored. Intravenous administration of liposomes containing crude "lymphokine" preparations was shown to significantly inhibit lung metastases in certain syngeneic mouse tumor systems. However, the lack of identity of the active component has remained a major drawback in the use of these preparations. We recently observed similar inhibition of lung metastases by treatment of tumor-bearing mice (fibrosarcoma T241 in C57BL/6 mice) with liposomes containing human C-reactive protein (CRP). To our knowledge, there have been no previously published studies of the effects of CRP on tumor growth and/or metastases. More recently, we have extended these studies to two other tumor systems (B16 melanoma and MCA-38 colon adenocarcinoma) in C57BL/6 mice and also observed inhibition of lung and liver metastases, respectively, by treatment with liposomes containing CRP. Thus, inhibition of metastases by CRP has now been observed in three entirely different tumor systems. Our studies have clinical relevance because, (a) the tumors employed spontaneously metastasize to the lungs or liver, two common sites of metastases for most human cancers, (b) CRP-liposome therapy eradicates established lung or liver metastases, and (c) the agent employed (CRP) is a normal serum component which is highly purified, well characterized and non-toxic. CRP is known to be present in a wide range of animal species, including certain ones not known to possess the immune system. However, the pathophysiological role of this molecule remains a mystery. Our studies suggest that CRP may have "biological response modifier' function of potential value in the therapy of metastatic disease. The specific aims of our project are: (1) to develop optimal conditions for CRP-liposome therapy in the three mouse tumor models described, (2) to carry out in vivo and in vitro experiments to explore the mechanism of tumor cell killing, and (3) to integrate the results of these studies to ultimatel;y pave the way for similar therapeutic studies in man.